ArticleFrontiers in psychiatry2026
Association between changes in estradiol, serotonin, and BDNF and antidepressant response in perimenopausal depression: a retrospective cohort study comparing integrated TCM-acupuncture with SSRIs.
Article in Frontiers in psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Perimenopausal depression (PMD) involves complex neuroendocrine interactions among estradiol (E Methods: We conducted a single-center retrospective cohort study in 240 perimenopausal women (TCM-Acu, n = 120; SSRIs, n = 120) treated for a minimum of eight weeks. Treatment effects were estimated using multivariable-adjusted regression (ANCOVA) accounting for baseline imbalances in age, disease duration, HAMD-17 score, and other covariates. Biomarker associations were examined via treatment × ΔBiomarker interaction terms. Results: In multivariable-adjusted analyses, TCM-Acu was associated with significantly greater HAMD-17 improvement relative to SSRIs (adjusted β = 3.79 points, 95% CI 2.79-4.79; P < 0.001; unadjusted mean change: 7.07 vs. 3.24 points). However, absolute treatment response rates (≥50% HAMD-17 reduction) were low in both groups (14.2% vs. 5.0%), indicating the observed difference reflects a relative rather than absolute clinical advantage. TCM-Acu was also associated with greater increases in 5-HT (adjusted β = 9.24 ng/mL, 95% CI 6.92-11.56; P < 0.001) and BDNF (adjusted β = 1.60 ng/mL, 95% CI 0.95-2.25; P < 0.001). Unadjusted estradiol levels did not differ significantly between groups (P = 0.592). Across the full cohort, changes in 5-HT and BDNF were positively associated with HAMD-17 improvement (Spearman ρ = 0.31 and 0.37, respectively), with the BDNF-HAMD-17 association being more pronounced in the TCM-Acu group on interaction testing. Conclusion: In multivariable-adjusted analyses, TCM-Acu was associated with greater HAMD-17 improvement and more pronounced increases in 5-HT and BDNF compared to SSRIs, while both treatments showed minimal differential effects on estradiol. However, absolute response rates were low in both groups, and the between-group difference reflects a relative rather than absolute clinical advantage. These observational findings are consistent with-but do not establish-the hypothesis that TCM-Acu's antidepressant associations may be mediated primarily through serotonergic and neurotrophic pathways; this requires prospective confirmation. Key limitations include the retrospective single-center design, baseline imbalances, absence of a sham acupuncture control, and differential treatment durations, which collectively preclude causal inference.
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